Leukocyte trafficking between stromal compartments: lessons from rheumatoid arthritis

The trafficking of leukocytes from their site of production in the bone marrow through the circulation and into peripheral tissues is a highly coordinated and tightly regulated process in healthy individuals. Lymphocytes are long-lived cells that visit many lymphoid and peripheral tissues over their lifetime and can even recirculate back to the bone marrow, whereas granulocytes and monocytes are not thought to recirculate so widely. Using rheumatoid arthritis (RA) as an example, this Review explores the migratory journey of leukocytes during the establishment and resolution of disease — from the blood, through the lymphoid tissues and into peripheral sites such as the lungs and the gut before their entry into the synovium. This Review explores our current understanding of differences in the molecular processes that regulate leukocyte trafficking at different phases of disease and in different stromal compartments, which could help to explain the disease heterogeneity seen in patients with RA. Expanding our knowledge of these processes will open new avenues in the clinical management of RA, paving the way for personalized medicine that is founded on the pathological molecular signature of each patient, which varies according to their phase of disease or disease subtype.